| 1. |
- Braun, Matthias, et al.
(författare)
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Changes of glacial front positions of Vestfonna (Nordaustlandet, Svalbard)
- 2011
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Ingår i: Geografiska Annaler. Series A, Physical Geography. - : Informa UK Limited. - 0435-3676 .- 1468-0459. ; 93:4, s. 301-310
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Tidskriftsartikel (refereegranskat)abstract
- Glaciers in Svalbard have shown considerable mass loss in recent years with a reported acceleration in the western and southern parts of the archipelago. However, for the ice cap Vestfonna, in northeastern Svalbard, climatic mass balance modelling has suggested almost balanced conditions over a period of nine years (2000–2009). A slightly positive geodetic mass balance (1990–2005) has been reported from a comparison of laser altimetry to older DEMs. A heterogeneous situation has been depicted for the various catchments, and hence changes in glacier extent can reveal additional information of glacier status, in particular when dealing with surge-type glaciers. We analysed a 34-year data record of multi-spectral satellite imagery in order to study changes in glacier frontal positions of the ice cap Vestfonna. A consistent pattern of almost steady retreat of the southern and north-eastern outlet glaciers of the ice cap is observed while Franklinbreen, the only major outlet glacier draining towards the north-west shows re-advance. This is consistent with an observed speed up and potential upcoming surge of this outlet. The glacier retreat on the southern coast also agrees with ICESat elevation change measurements. However, due to the glacier response time no direct relations between frontal retreat and surface mass balance can be drawn from the short observation period. The heterogeneous pattern of changes with on-going dynamic adjustments in some areas make the ice cap Vestfonna an ideal test site for future monitoring activities including novel techniques like differential interferometry from bi-static SAR systems.
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| 2. |
- Hertwig, Falk, et al.
(författare)
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Definition of Genetic Events Directing the Development of Distinct Types of Brain Tumors from Postnatal Neural Stem/Progenitor Cells.
- 2012
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Ingår i: Cancer Research. - 1538-7445. ; 72:13, s. 3381-3392
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Tidskriftsartikel (refereegranskat)abstract
- Although brain tumors are classified and treated based upon their histology, the molecular factors involved in the development of various tumor types remain unknown. In this study, we show that the type and order of genetic events directs the development of gliomas, central nervous system primitive neuroectodermal tumors, and atypical teratoid/rhabdoid-like tumors from postnatal mouse neural stem/progenitor cells (NSC/NPC). We found that the overexpression of specific genes led to the development of these three different brain tumors from NSC/NPCs, and manipulation of the order of genetic events was able to convert one established tumor type into another. In addition, loss of the nuclear chromatin-remodeling factor SMARCB1 in rhabdoid tumors led to increased phosphorylation of eIF2α, a central cytoplasmic unfolded protein response (UPR) component, suggesting a role for the UPR in these tumors. Consistent with this, application of the proteasome inhibitor bortezomib led to an increase in apoptosis of human cells with reduced SMARCB1 levels. Taken together, our findings indicate that the order of genetic events determines the phenotypes of brain tumors derived from a common precursor cell pool, and suggest that the UPR may represent a therapeutic target in atypical teratoid/rhabdoid tumors. Cancer Res; 72(13); 3381-92. ©2012 AACR.
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| 3. |
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| 4. |
- Jones, Robert P., et al.
(författare)
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Patterns of Recurrence After Resection of Pancreatic Ductal Adenocarcinoma : A Secondary Analysis of the ESPAC-4 Randomized Adjuvant Chemotherapy Trial
- 2019
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Ingår i: JAMA Surgery. - : AMER MEDICAL ASSOC. - 2168-6254 .- 2168-6262. ; 154:11, s. 1038-1048
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Tidskriftsartikel (refereegranskat)abstract
- Importance: The patterns of disease recurrence after resection of pancreatic ductal adenocarcinoma with adjuvant chemotherapy remain unclear.Objective: To define patterns of recurrence after adjuvant chemotherapy and the association with survival.Design, Setting, and Participants: Prospectively collected data from the phase 3 European Study Group for Pancreatic Cancer 4 adjuvant clinical trial, an international multicenter study. The study included 730 patients who had resection and adjuvant chemotherapy for pancreatic cancer. Data were analyzed between July 2017 and May 2019.Interventions: Randomization to adjuvant gemcitabine or gemcitabine plus capecitabine.Main Outcomes and Measures: Overall survival, recurrence, and sites of recurrence.Results: Of the 730 patients, median age was 65 years (range 37-81 years), 414 were men (57%), and 316 were women (43%). The median follow-up time from randomization was 43.2 months (95% CI, 39.7-45.5 months), with overall survival from time of surgery of 27.9 months (95% CI, 24.8-29.9 months) with gemcitabine and 30.2 months (95% CI, 25.8-33.5 months) with the combination (HR, 0.81; 95% CI, 0.68-0.98; P=.03). The 5-year survival estimates were 17.1% (95% CI, 11.6%-23.5%) and 28.0% (22.0%-34.3%), respectively. Recurrence occurred in 479 patients (65.6%); another 78 patients (10.7%) died without recurrence. Local recurrence occurred at a median of 11.63 months (95% CI, 10.05-12.19 months), significantly different from those with distant recurrence with a median of 9.49 months (95% CI, 8.44-10.71 months) (HR, 1.21; 95% CI, 1.01-1.45; P=.04). Following recurrence, the median survival was 9.36 months (95% CI, 8.08-10.48 months) for local recurrence and 8.94 months (95% CI, 7.82-11.17 months) with distant recurrence (HR, 0.89; 95% CI, 0.73-1.09; P=.27). The median overall survival of patients with distant-only recurrence (23.03 months; 95% CI, 19.55-25.85 months) or local with distant recurrence (23.82 months; 95% CI, 17.48-28.32 months) was not significantly different from those with only local recurrence (24.83 months; 95% CI, 22.96-27.63 months) (P=.85 and P=.35, respectively). Gemcitabine plus capecitabine had a 21% reduction of death following recurrence compared with monotherapy (HR, 0.79; 95% CI, 0.64-0.98; P=.03).Conclusions and Relevance: There were no significant differences between the time to recurrence and subsequent and overall survival between local and distant recurrence. Pancreatic cancer behaves as a systemic disease requiring effective systemic therapy after resection.Trial Registration: ClinicalTrials.gov identifier: NCT00058201, EudraCT 2007-004299-38, and ISRCTN 96397434. This secondary analysis of a randomized clinical trial investigates patterns of recurrence after adjuvant chemotherapy in pancreatic cancer and the association with survival.
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| 5. |
- Noack, Sandra, et al.
(författare)
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Periostin Secreted by Mesenchymal Stem Cells Supports Tendon Formation in an Ectopic Mouse Model
- 2014
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Ingår i: Stem Cells and Development. - : Mary Ann Liebert Inc. - 1557-8534 .- 1547-3287. ; 23:16, s. 1844-1857
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Tidskriftsartikel (refereegranskat)abstract
- True tendon regeneration in human patients remains a vision of musculoskeletal therapies. In comparison to other mesenchymal lineages the biology of tenogenic differentiation is barely understood. Specifically, easy and efficient protocols are lacking that might enable tendon cell and tissue differentiation based on adult (stem) cell sources. In the murine mesenchymal progenitor cell line C3H10T1/2 overexpression of the growth factor bone morphogenetic protein 2 (BMP2) and a constitutively active transcription factor, Smad8 L + MH2, mediates tendon cell differentiation in vitro and the formation of tendon-like tissue in vivo. We hypothesized that during this differentiation secreted factors involved in extracellular matrix formation exert a major impact on tendon development. Gene expression analyses revealed four genes encoding secreted factors that are notably upregulated: periostin, C-type lectin domain family 3 (member b), RNase A4, and follistatin-like 1. These factors have not previously been implicated in tendon biology. Among these, periostin showed a specific expression in tenocytes of adult mouse Achilles tendon and in chondrocytes within the nonmineralized fibrocartilage zone of the enthesis with the calcaneus. Overexpression of periostin alone or in combination with constitutively active BMP receptor type in human mesenchymal stem cells and subsequent implantation into ectopic sites in mice demonstrated a reproducible moderate tenogenic capacity that has not been described before. Therefore, periostin may belong to the factors contributing to the development of tenogenic tissue.
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| 6. |
- Pfenninger, Cosima, et al.
(författare)
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CD133 is not present on neurogenic astrocytes in the adult subventricular zone, but on embryonic neural stem cells, ependymal cells, and glioblastoma cells
- 2007
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Ingår i: Cancer Research. - 1538-7445. ; 67:12, s. 5727-5736
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Tidskriftsartikel (refereegranskat)abstract
- Human brain tumor stem cells have been enriched using antibodies against the surface protein CD133. An antibody recognizing CD133 also served to isolate normal neural stem cells from fetal human brain, suggesting a possible lineage relationship between normal neural and brain tumor stem cells. Whether CD133-positive brain tumor stem cells can be derived from CD133-positive neural stem or progenitor cells still requires direct experimental evidence, and an important step toward such investigations is the identification and characterization of normal CD133-presenting cells in neurogenic regions of the embryonic and adult brain. Here, we present evidence that CD133 is a marker for embryonic neural stem cells, an intermediate radial glial/ependymal cell type in the early postnatal stage, and for ependymal cells in the adult brain, but not for neurogenic astrocytes in the adult subventricular zone. Our findings suggest two principal possibilities for the origin of brain tumor stem cells: a derivation from CD133-expressing cells, which are normally not present in the adult brain (embryonic neural stem cells and an early postnatal intermediate radial glial/ependymal cell type), or from CD133-positive ependymal cells in the adult brain, which are, however, generally regarded as postmitotic. Alternatively, brain tumor stem cells could be derived from proliferative but CD133-negative neurogenic astrocytes in the adult brain. In the latter case, brain tumor development would involve the production of CD133.
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| 7. |
- Pfenninger, Cosima, et al.
(författare)
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Prospectively isolated CD133/CD24-positive ependymal cells from the adult spinal cord and lateral ventricle wall differ in their long-term in vitro self-renewal and in vivo gene expression.
- 2011
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Ingår i: GLIA. - : Wiley. - 1098-1136 .- 0894-1491. ; 59:1, s. 68-81
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Tidskriftsartikel (refereegranskat)abstract
- In contrast to ependymal cells located above the subventricular zone (SVZ) of the adult lateral ventricle wall (LVW), adult spinal cord (SC) ependymal cells possess certain neural stem cell characteristics. The molecular basis of this difference is unknown. In this study, antibodies against multiple cell surface markers were applied to isolate pure populations of SC and LVW ependymal cells, which allowed a direct comparison of their in vitro behavior and in vivo gene expression profile. Isolated CD133(+)/CD24(+)/CD45(-)/CD34(-) ependymal cells from the SC displayed in vitro self-renewal and differentiation capacity, whereas those from the LVW did not. SC ependymal cells showed a higher expression of several genes involved in cell division, cell cycle regulation, and chromosome stability, which is consistent with a long-term self-renewal capacity, and shared certain transcripts with neural stem cells of the embryonic forebrain. They also expressed several retinoic acid (RA)-regulated genes and responded to RA exposure. LVW ependymal cells showed higher transcript levels of many genes regulated by transforming growth factor-β family members. Among them were Dlx2, Id2, Hey1, which together with Foxg1 could explain their potential to turn into neuroblasts under certain environmental conditions. © 2010 Wiley-Liss, Inc.
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| 8. |
- Prost, Gaëlle, et al.
(författare)
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The putative tumor suppressor gene EphA7 is a novel BMI-1 target
- 2016
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Ingår i: Oncotarget. - : Impact Journals, LLC. - 1949-2553. ; 7:36, s. 58203-58217
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Tidskriftsartikel (refereegranskat)abstract
- Bmi1 was originally identified as a gene that contributes to the development of mouse lymphoma by inhibiting MYC-induced apoptosis through repression of Ink4a and Arf. It codes for the Polycomb group protein BMI-1 and acts primarily as a transcriptional repressor via chromatin modifications. Although it binds to a large number of genomic regions, the direct BMI-1 target genes described so far do not explain the full spectrum of BMI-1-mediated effects. Here we identify the putative tumor suppressor gene EphA7 as a novel direct BMI-1 target in neural cells and lymphocytes. EphA7 silencing has been reported in several different human tumor types including lymphomas, and our data suggest BMI1 overexpression as a novel mechanism leading to EphA7 inactivation via H3K27 trimethylation and DNA methylation.
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| 9. |
- Rahimi, Jaber, et al.
(författare)
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Modeling gas exchange and biomass production in West African Sahelian and Sudanian ecological zones
- 2021
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Ingår i: Geoscientific Model Development. - : Copernicus GmbH. - 1991-959X .- 1991-9603. ; 14:6, s. 3789-3812
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Tidskriftsartikel (refereegranskat)abstract
- West African Sahelian and Sudanian ecosystems provide essential services to people and also play a significant role within the global carbon cycle. However, climate and land use are dynamically changing, and uncertainty remains with respect to how these changes will affect the potential of these regions to provide food and fodder resources or how they will affect the biosphere-atmosphere exchange of CO2. In this study, we investigate the capacity of a process-based biogeochemical model, LandscapeDNDC, to simulate net ecosystem exchange (NEE) and aboveground biomass of typical managed and natural Sahelian and Sudanian savanna ecosystems. In order to improve the simulation of phenology, we introduced soil-water availability as a common driver of foliage development and productivity for all of these systems. The new approach was tested by using a sample of sites (calibration sites) that provided NEE from flux tower observations as well as leaf area index data from satellite images (MODIS, MODerate resolution Imaging Spectroradiometer). For assessing the simulation accuracy, we applied the calibrated model to 42 additional sites (validation sites) across West Africa for which measured aboveground biomass data were available. The model showed good performance regarding biomass of crops, grass, or trees, yielding correlation coefficients of 0.82, 0.94, and 0.77 and root-mean-square errors of 0.15, 0.22, and 0.12gkggm-2, respectively. The simulations indicate aboveground carbon stocks of up to 0.17, 0.33, and 0.54gkggCgha-1gm-2 for agricultural, savanna grasslands, and savanna mixed tree-grassland sites, respectively. Carbon stocks and exchange rates were particularly correlated with the abundance of trees, and grass biomass and crop yields were higher under more humid climatic conditions. Our study shows the capability of LandscapeDNDC to accurately simulate carbon balances in natural and agricultural ecosystems in semiarid West Africa under a wide range of conditions; thus, the model could be used to assess the impact of land-use and climate change on the regional biomass productivity.
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